Epilepsy and Learning Disability

Wessex Epilepsy Interest group

24th June 2011

Learning difficulties and epilepsy

Major co-morbidity
Complex association

Often un-noticed Vast differential diagnosis of aetiology Is it only a problem in the symptomatic group? Epileptic encephalopathy Will it get better if the seizures go away? Is it epilepsy??

Epilepsy- epidemiology
Prevalence rates 3.6-6.5/1000 in Europe Increased risk of 11% with either CP or LD
LD, IQ50-70: 15%, IQ<50: 30%

LD and concurrent CP increases risk of epilepsy to 48% Neurocutaneous syndromes associated with very high rates of epilepsy
91% in Tuberous Sclerosis

Cerebral palsy
Risks of epilepsy: 4 limb involvement 50-94% Hemiplegia 22-47% Diplegia 16-27% EEG abnormalities common in children with CP +/- epilepsy

The epileptic encephalopathies

Definition: A condition in which the epileptiform abnormalities are believed to contribute to progressive disturbance in cerebral function

Epileptic encephalopathy
Neonatal syndromes West syndrome
2/3 severe cognitive and psychological impairment 5-12% normal cognitive development

Dravet syndrome Myoclonic astatic syndrome Landau-Kleffner syndrome Lennox Gastaut syndrome.

West syndrome- prognosis

Prognosis is determined nearly exclusively by the causative factors and their severity. The spasms themselves and their response to treatment may not have prognostic significance
Panayiotopoulos

Epilepsy in Infancy study

Developmental abilities approximately 3 months after diagnosis are predictive of subsequent developmental ability at 12 months follow up. Children with structural brain abnormalities have a reduction in developmental cognitive score over time Seizure status does not influence cognitive outcome 1 year after diagnosis

LGS - prognosis
Poor outcome associated with:
Early age of onset Symptomatic aetiology Frequent tonic seizures Repeated episodes of NCS Consistently slow EEG background

Aetiology
Learning difficulties

Seizures

Aetiology???????????
Dilemma regarding diagnosis.

Aetiology
Genetic Metabolic Structural Neurocutaneous Tumour Infective Immune mediated
Gene mutations
Sodium channel/ SCN1A

Chromosomal
1p36, Wolf-Hirschhorn T21, Angelman syndrome Fragile X Ring chromosome 20

Chromosome array testing..

Aetiology
Genetic Metabolic Structural Neurocutaneous Tumour Infective Immune mediated
Mitochondrial Biotinidase deficiency Peroxisomal Lysosomal Creatine disorders Purine disorders Amino/organic acids Vitamin responsive epilepsies .

Aetiology
Genetic Metabolic Structural Neurocutaneous Tumour Infective Immune mediated

Perisylvian syndromes Hemimegalencephaly

Periventricular And nodular heterotpia

Aetiology
Genetic Metabolic Structural Neurocutaneous Tumour Infective Immune mediated

Aetiology
Genetic Metabolic Structural Neurocutaneous Tumour Infective Immune mediated

Aetiology
Genetic Metabolic Structural Neurocutaneous Tumour Infective Immune mediated

Aetiology
Genetic Metabolic Structural Neurocutaneous Tumour Infective Immune mediated NMDAR VGK GAD Hashimoto encephalitis Rassmussen encephalitis

Some syndromes.

Electrical Status Epilepticus in Slow wave sleep

NREM

REM

Electrical Status Epilepticus in Slow wave sleep

Triad of:
Continuous spike and slow wave activity in NREM sleep Seizures Neuropsychological and motor impairment

ESES
Age dependant
ONLY occurs in childhood

3 stages
Initial seizures, often nocturnal and focal
Benign and symptomatic aetiology

ESES starts 1-2 years after initial seizure Remission months-7 years from onset

Seizures in ESES
Habitual seizures and new seizures emerge.. Hemi-clonic , GTCS [mostly nocturnal] typical/atypical absences, atonic, myoclonus, NCSE
Most children have numerous, frequent seizures

Negative myoclonus

Neuropsychology of ESES
Dramatic decline in cognitive abilities Deficit dependant on spike localisation
Frontal
Executive functioning, language, behaviour

Opercular
Drooling, dysarthria, speech arrest

Temporal
Linguistic difficulties

Duration of ESES related to final neuropsychological functioning

Motor effects of ESES

Ataxia Dyspraxia

Hemiparesis

Treatment of ESES
Sodium valproate, LVT, LTG
Benzodiazepines Steroids Multiple subpial transection in LKS

Landau-Kleffner syndrome
Acquired epileptic aphasia
Onset age 2-8 years M>F

Partly reversible epileptic encephalopathy Cognitive/behavioural/neuropsychological difficulties +/-Seizures

LKS- linguistic difficulties

Auditory verbal agnosia
Unable to understand linguistic sounds May progress to inability to make sense of nonlinguistic sounds

Mistaken as deafness, mutism, autism Affects other linguistic functions

Expressive speech Perseverations jargon speech

May become entirely mute May be fluctuating in nature

LKS- cognitive/behavioural
Cognitive and behavioural difficulties common ADHD/ hyperactivity Rarely psychosis Variable

LKS- seizures
In 75% Infrequent, usually well controlled Various seizure types
GTCS Focal seizure Atonic

Often nocturnal Remit before age 15y

LKS- pathophysiology
Functional epileptogenic lesion in eloquent speech area MRI usually normal Occur at a critical age of brain development Aggressive epileptic activity in the dominant temporal lobe detrimental to establishment of appropriate neuronal connections

LKS

?
Language impairment
BECTS LKS

LKS - EEG
Posterior temporal foci +/- multifocal sharp/spikes, bisynchronous activity
Markedly facilitated by NREM sleep

ESES at some point in most cases

LKS - prognosis
EEG abnormalities and seizures age dependant Remit by 15 years Cognitive and language improves as EEG normalises Influenced by duration of ESES and age of onset 10-20% achieve complete normalisation

Autism-epilepsy connection
Prevalence of epilepsy in children with autism 5-38% Bimodal incidence
Infancy - 5years 2nd peak in adolescence [>10y]

Risk of epilepsy higher in children with severe LD

Cumulative probability of epilepsy 8% at 10 yrs normal cognition, 27% at 10 years if SLD

Epilepsy persists into adult life

EEG in autism
EEG abnormalities frequently seen in the absence of clinical seizures
18.9% in a study of 106 people with autism 331 yrs of age 21-68% have epileptiform sleep EEG

Usually focal spikes, may be multifocal Abnormalities frequently similar to those seen in benign focal epilepsies of childhood

Autism and epilepsy..

? Autism and epilepsy both different clinical manifestations of the same brain pathology [fragile X, TSC] ? Temporal lobe dysfunction
Higher rates of autism in TLE

Autism an end result of epileptic encephalopathy ie, West syndrome, LGS, Dravet syndrome
Epilepsy early in brain development affects neuronal networks

Should we do an EEG in children with autistic regression?

No evidence that epilepsy is a risk factor for autistic regression LKS/ESES may be misdiagnosed as autism but phenotype distinctly different

Rett syndrome
Background EEG becomes epileptiform Epileptic and non-epileptic events
Stereotypies Hyperventilation Dystonia

Genetics:
MECP2
80% of cases

CDKL5
Early onset seizures, infantile spasms, tonic and focal seizures

The child with severe learning disability and epilepsy

Is it epilepsy??? ? Mixed epileptic and non-epileptic events
Staring spells Stiffenings Stereotypies NEAD

The child with severe learning disability and epilepsy

What are the seizure types? What is the epilepsy syndrome?
Correct AED Awareness of AEDs that may exacerbate behavioural problems
LVT

Avoid polypharmacy ? Non-medical treatment options..

The child with severe learning disability and epilepsy

What is the aetiology?
? Focal brain lesion ? Epilepsy surgery an option
LD is NOT a contraindication for surgery

The child with severe learning disability and epilepsy

What are the co-morbidities?

Behaviour Psychological

Sleep

The co-morbidity of childhood epilepsy

The Isle of Wight study, Rutter et al, 1970 Rate of psychiatric disorder
In the general population: 7% Children with physical disorder outside the CNS: 12% Children with idiopathic seizures: 29% Children with structural brain abnormalities: 38% Children with seizures AND structural brain abnormalities: 58%

A population survey of mental health problems in children with epilepsy

[Goodman et al, Dev Med and Child Neurol, 2003]

Rates of DSM IV psychiatric disorder

37% epilepsy 11% diabetes 9% in 10202 control children

Both uncomplicated and complicated epilepsy groups have increase in emotional and behavioural disorders Only the complicated group was associated with significant increase rate of hyperactive and pervasive developmental disorders

Adolescence

Social stigma

Self Esteem

Family and Social factors Education Learning disability

Psychopathology In childhood epilepsy AEDs

Polypharmacy

Seizure Seizure control type Sleep

Structural Brain abnormality

Sleep disorders are more common in children with epilepsy [stores et al, 1998]
79 children with epilepsy, 73 controls

Higher rates in children with epilepsy of:

Poor quality sleep Anxieties regarding sleep Sleep disordered breathing Short duration sleep

?contributor to the learning and behavioural difficulties

Summary
Relationship between epilepsy and learning disability complex and reciprocal Some epileptic encephalopathies may be treatable Management requires a structured and holistic approach

Questions???